ABSTRACT
BACKGROUND: Proteasome assembly chaperone 3 (PSMG3), a subunit of proteasome, has been found to be associated with lung cancer. However, the role of PSMG3 in other cancers has not been elucidated. The objective of this study was to explore the immune role of PSMG3 in pan-cancer and confirm the oncogenic significance in liver hepatocellular carcinoma (LIHC). METHODS: We examined the differential expression of PSMG3 across various cancer types using data from The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) databases. We investigated the prognostic value of PSMG3 and examined its relationship with tumor mutation burden (TMB), microsatellite instability (MSI), and immune infiltration. The functional enrichment analysis was performed to explore the potential molecular mechanism of PSMG3. To elucidate the biological function of PSMG3, we conducted in vitro experiments using liver cancer cell lines. RESULTS: PSMG3 was highly expressed in most cancers. The high PSMG3 expression value of PSMG3 was closely related to poor prognosis. We observed correlations between PSMG3 and TMB, and MSI immune infiltration. PSMG3 may be involved in metabolic reprogramming, cell cycle, and PPAR pathways. The over-expression of PSMG3 promoted the proliferation, migration, and invasion capabilities of liver cancer cells. CONCLUSION: Our study demonstrated that PSMG3 was a pivotal oncogene in multiple cancers. PSMG3 contributed to the progression and immune infiltration in pan-cancer, especially in LIHC.
ABSTRACT
INTRODUCTION: Fungal infections are caused by a broad range of pathogenic fungi that are found worldwide with different geographic distributions, incidences, and mortality rates. Considering that there are relatively few approved medications available for combating fungal diseases and no vaccine formulation commercially available, multiple groups are searching for new antifungal drugs, examining drugs for repurposing and developing antifungal vaccines, in order to control deaths, sequels, and the spread of these complex infections. AREAS COVERED: This review provides a summary of advances in fungal vaccine studies and the different approaches under development, such as subunit vaccines, whole organism vaccines, and DNA vaccines, as well as studies that optimize the use of adjuvants. We conducted a literature search of the PubMed with terms: fungal vaccines and genus of fungal pathogens (Cryptococcus spp. Candida spp. Coccidioides spp. Aspergillus spp. Sporothrix spp. Histoplasma spp. Paracoccidioides spp. Pneumocystis spp. and the Mucorales order), a total of 177 articles were collected from database. EXPERT OPINION: Problems regarding the immune response development in an immunocompromised organism, the similarity between fungal and mammalian cells, and the lack of attention by health organizations to fungal infections are closely related to the fact that, at present, there are no fungal vaccines available for clinical use.
Subject(s)
Mycoses , Vaccines , Animals , Humans , Antifungal Agents/therapeutic use , Fungi , Mycoses/prevention & control , Mycoses/drug therapy , Mycoses/epidemiology , Vaccines/therapeutic use , Vaccine Development , MammalsABSTRACT
ABSTRACT Objective: To evaluate the effect of colostrum therapy on days to start a suckling diet in newborns diagnosed with simple gastroschisis. Methods: Randomized clinical trial with newborns diagnosed with simple gastroschisis at a federal hospital in Rio de Janeiro who were randomized to receive oropharyngeal administration of 0.2mL of colostrum or a "sham procedure" during the first 3 days of life. The analysis included clinical outcomes such as days without food, days with parenteral feeding, days until the start of enteral feeding, days to reach complete enteral feeding, sepsis and length of hospital stay. Results: The onset of oral feeding (suction) in patients with simple gastroschisis in both groups occurred at a median of 15 days. Conclusion: The present study showed that there were no significant differences in the use of colostrum therapy and the number of days to the start of enteral feeding and suction diet between groups of newborns with simple gastroschisis.
RESUMO Objetivo: Avaliar o efeito da colostroterapia em dias para iniciar a dieta por sucção em recém-nascidos com diagnóstico de gastrosquise simples. Métodos: Ensaio clínico randomizado com recém-nascidos diagnosticados com gastrosquise simples em um hospital federal no Rio de Janeiro que foram randomizados para receber administração orofaríngea de 0,2mL de colostro ou "procedimento simulado", nos primeiros 3 dias de vida. A análise incluiu desfechos clínicos, como dias sem alimentação, dias com alimentação parenteral, dias para iniciar a alimentação enteral, dias para atingir a alimentação completa, sepse e tempo de internação. Resultados: O início da alimentação por via oral (sucção) na gastrosquise simples, em ambos os grupos, ocorreu com mediana de 15 dias. Conclusão: O presente estudo mostrou que não há diferenças significativas no uso de colostroterapia em dias para início de alimentação enteral e dieta por sucção entre grupos de recém-nascidos com gastrosquise simples.
ABSTRACT
Advances in the treatment of rare tumors like penile cancer were always hampered by the lack of deep comprehension of the molecular biology and genomic and epigenomic alterations involved in carcinogenesis and tumor progression, as well as by the difficulty in recruitment of patients for prospective clinical trials. Despite the high rates of cure in early localized penile cancers with surgery or other local procedures, locally advanced and metastatic tumors require systemic treatment, with chemotherapy being the current standard, but with high toxicity and no proven real impact on survival. Recent important findings of frequent genomic alterations and mutation signatures in penile cancer have motivated several trials in new modalities of systemic treatments, especially immunotherapy. This review aims to present the most recent advances and the prospect of new modalities of systemic therapies with ongoing studies in penile cancer.
ABSTRACT
BACKGROUND: COVID-19 high-titer CCP selection is a concern, because neutralizing antibody (nAb) testing requires sophisticated labs and methods. Surrogate tests are an alternative for measuring nAb levels in plasma bags, including those that are pathogen-reduced. STUDY DESIGN/METHODS: We studied a panel consisting of 191 samples from convalescent donors tested by nAb (CPE-VNT), obtained from 180 CCP donations (collection: March 20-January 21) and 11 negative controls, with a total of 80 and 111 serum and plasma samples (71 amotosalen/UV treated), with nAb titers ranging from negative to 10,240. Samples were blindly tested for several surrogates: one anti-RBD, two anti-spike, and four anti-nucleocapsid tests, either isolated or combined to improve their positive predictive values as predictors of the presence of high-titer nAbs, defined as those with titers ≥160. RESULTS: Except for combined and anti-IgA/M tests, all isolated surrogate tests showed excellent performance for nAb detection: sensitivity (98.3%-100%), specificity (85.7%-100%), PPV (98.9%-100%), NPV (81.3%-100%), and AUC (0.93-0.96), with a variable decrease in sensitivity and considerably lower specificity when using FDA authorization and concomitant nAb titers ≥160. All surrogates had AUCs that were statistically different from CPE-VNT if nAb≥160, including when using combined, orthogonal approaches. CONCLUSIONS: Surrogate tests (isolated or in combination) have an indirect good performance in detecting the presence of nAb, with lower sensitivity and specificity when high nAb titer samples are used, possibly accepting a considerable number of donors whose nAb titers are actually low, which should be evaluated by each laboratory responsible for CCP collection.
Subject(s)
Antibodies, Neutralizing/therapeutic use , Antibodies, Viral/therapeutic use , COVID-19/therapy , Blood Donors , Humans , Immunization, Passive , SARS-CoV-2 , COVID-19 SerotherapyABSTRACT
PURPOSE: Tryptophan metabolites have immunomodulatory functions, suggesting possible roles in cancer immunity. METHODS: Plasma tryptophan metabolites were measured using liquid chromatography/mass spectrometry before immune checkpoint inhibitors (ICIs) in patients with non-small cell lung cancer (NSCLC). RESULTS: The 19 patients with NSCLC had significantly lower levels of tryptophan (p = 0.002) and xanthurenic acid (p = 0.032), and a significantly higher level of 3-hydroxyanthranilic acid (3-HAA) (p = 0.028) compared with the 10 healthy volunteers. The patients achieving objective responses had significantly lower levels of 3-HAA than those who did not (p = 0.045). Receiver operating characteristic analyses determined that the cutoff value of 3-HAA for objective response was 35.4 pmol/mL (sensitivity: 87.5% and specificity: 83.3%). The patients with 3-HAA < 35.4 pmol/mL had significantly longer median progression-free survival (7.0 months) than those without (1.6 months, p = 0.022). CONCLUSIONS: Tryptophan metabolites may have a potential for predicting the efficacy of ICIs. REGISTRATION NUMBER: University Hospital Medical Information Network Clinical Trial Registry 000026140.
Subject(s)
3-Hydroxyanthranilic Acid/analysis , Carcinoma, Non-Small-Cell Lung/blood , Immune Checkpoint Inhibitors/therapeutic use , Lung Neoplasms/blood , Tryptophan/blood , Xanthurenates/blood , Adult , Aged , Aged, 80 and over , B7-H1 Antigen/blood , B7-H1 Antigen/metabolism , Biomarkers/blood , Biomarkers/metabolism , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/mortality , Female , Humans , Lung Neoplasms/drug therapy , Lung Neoplasms/mortality , Male , Middle Aged , Progression-Free Survival , Prospective Studies , ROC Curve , Regression Analysis , Sensitivity and Specificity , Treatment Outcome , Tryptophan/metabolismABSTRACT
The upregulation of co-inhibitory checkpoint receptors/ligands that inactivate antitumor T-cells, the enhancement of Tregs-mediated trogocytosis that contribute delayed maturation of antigen presenting cell (APC), and the high Tregs/CD+8 ratio that maintained low threshold of CD+8 cells in the tumor microenvironment (TME); all represent the nuances in the immune evasive strategies of pancreatic ductal adenocarcinoma (PDAC). PDAC is the most aggressive type of pancreatic cancers characterized by poor prognosis and extremely low survivability. Over the years, fraternity of scientists have developed therapeutic agents that can bolster the capacity of the antitumor immunity, usually via the inhibition of immune checkpoints. While this immune checkpoint inhibition therapy represents one major jab from immunity to PDAC, this cancer remains highly resistant due to the acme of desmoplasia in its TME. In this review, we discuss the mechanisms of various checkpoint receptors/ligands axes that are relevant to the fitness of PDAC in its oncogenic ring. These checkpoints include PD-1, CTLA-4, ICOS, TIM-3, TIGIT, BTLA, BTN3A, and VISTA. In addition, we provided evidences that are relevant to the understanding of immune checkpoint inhibition, with extensive outline of immune checkpoint inhibitors that are critical to the treatment of PDAC. Finally, we discuss recently known intricacies of PDAC-mediated immunosuppression, and current advances in treatment options. Having realized that the overall scenario between PDAC and antitumor immunity is like the throwing of jabs in a ring, we therefore discuss future directions and prospect that can knock out PDAC in favor of immunity and humanity.
Subject(s)
B7-H1 Antigen/genetics , CTLA-4 Antigen/genetics , Carcinoma, Pancreatic Ductal/drug therapy , Immune Checkpoint Inhibitors/therapeutic use , Programmed Cell Death 1 Receptor/genetics , Antigen-Presenting Cells/drug effects , Antigen-Presenting Cells/immunology , B7-H1 Antigen/immunology , CTLA-4 Antigen/antagonists & inhibitors , Carcinogenesis/drug effects , Carcinoma, Pancreatic Ductal/immunology , Carcinoma, Pancreatic Ductal/pathology , Humans , Immunotherapy/methods , Programmed Cell Death 1 Receptor/immunology , T-Lymphocytes/drug effects , T-Lymphocytes/immunology , T-Lymphocytes, Regulatory/drug effects , T-Lymphocytes, Regulatory/immunology , Tumor Microenvironment/drug effects , Tumor Microenvironment/immunologyABSTRACT
INTRODUCTION: Immune checkpoint inhibitor-related pneumonitis (ICIP) is a potentially life threatening immune-related adverse event (irAE), especially in non-small cell lung cancer (NSCLC) patients. Currently, the potential for increased irAE in patients who receive radiotherapy is scarcely known, although a connection between antitumor immune responses and irAEs has been suggested. In this study, we evaluated the development of ICIP in non-small cell lung cancer patients with prior radiotherapy, treated with immunotherapy in the second-line. METHODS: In this retrospective trial, we included patients treated with second-line immunotherapy at the National Cancer Institute in Mexico City from February 2015 to February 2018. Clinical, radiological and treatment variables were evaluated according to the presence of ICIP as defined by the Common Terminology Criteria for Adverse Events (4.0) in patients with or without a previous (≥months) history of radiotherapy. RESULTS: Among 101 NSCLC patients who received treatment with ICIs, 22 patients (21.8%) were diagnosed with ICIP, of which 73% (16/22) had a history of radiotherapy (OR 6.04, 95% CI 2.03-18.0, p < 0.001). Median progression free survival and overall survival were similar in patients who developed ICIP compared with those who did not, however, patients who presented grade ≥ 2 ICIP had an increased risk of mortality (HR 2.54, 95% CI 1.20-5.34, p = 0.014). CONCLUSION: In this real-world cohort of NSCLC patients treated with ICI, the history of prior radiotherapy was associated with increased risk for ICIP development. Unlike other irAEs, grade ≥ 2 ICIP is an independent prognostic factor for decreased survival in NSCLC patients.
ABSTRACT
BACKGROUND: Coronavirus disease 2019 (COVID-19) convalescent plasma (CCP) collection began in two Brazilian hospitals for treatment of severe/critical patients. METHODS AND MATERIALS: Mild/moderate COVID-19 convalescents were selected as CCP donors after reverse transcription polymerase chain reaction (RT-PCR) confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and absence of symptoms for ≥14 days plus (a) age (18-60 years), body weight greater than 55 kg; (b) immunohematological studies; (c) no infectious markers of hepatitis B virus, hepatitis C virus, human immunodeficiency virus, human T-lymphotropic virus-1/2, Chagas and syphilis infection; (d) no HLA antibodies (multiparous); (e) second RT-PCR (nasopharyngeal swab and/or blood) negativity; (f) virus neutralization test (cytopathic effect-based virus neutralization test neutralizing antibody) and anti-nucleocapsid protein SARS-CoV-2 IgM, IgG, and IgA enzyme-linked immunosorbent assays. RESULTS: Among 271 donors (41 females, 230 males), 250 presented with neutralizing antibodies. Final RT-PCR was negative on swab (77.0%) or blood (88.4%; P = .46). Final definition of RT-PCR was only defined at more than 28 days after full recovery in 59 of 174 (33.9%) RT-PCR -ve, and 25/69 RT-PCR +ve (36.2%; 13 between 35 and 48 days). Neutralizing antibody titers of 160 or greater were found in 63.6%. Correlation between IgG signal/cutoff of 5.0 or greater and neutralizing antibody of 160 or greater was 82.4%. Combination of final RT-PCR -ve with neutralizing antibody ≥160 was 41.3% (112/271). Serial plasma collection showed decline in neutralizing antibody titers and IgA levels (P < .05), probably denoting a "golden period" for CCP collection (≤28 days after joining the program); IgA might have an important role as neutralizing antibody. Donor's weight, days between disease onset and serial plasma collection, and IgG and IgM levels are important predictors for neutralizing antibody titer. CONCLUSIONS: RT-PCR +ve cases are still detected in 36.2% within 28 to 48 days after recovery. High anti-nucleocapsid protein IgG levels may be used as a surrogate marker to neutralizing antibody.
Subject(s)
Antibodies, Neutralizing/blood , Antibodies, Viral/blood , COVID-19 Serological Testing , COVID-19/blood , COVID-19/therapy , Convalescence , Donor Selection/statistics & numerical data , SARS-CoV-2/immunology , Adult , Blood Donors , Brazil/epidemiology , COVID-19/immunology , COVID-19 Nucleic Acid Testing , Enzyme-Linked Immunosorbent Assay , Female , Humans , Immunization, Passive , Immunoglobulin A/blood , Immunoglobulin G/blood , Immunoglobulin M/blood , Male , Middle Aged , Reverse Transcriptase Polymerase Chain Reaction , SARS-CoV-2/isolation & purification , Time Factors , Young Adult , COVID-19 SerotherapyABSTRACT
BACKGROUND: Clear cell renal cell carcinoma (ccRCC), the most aggressive renal cancer, is characterized by early lymph node metastases and bad prognosis. Most therapies targeting advanced or metastatic ccRCC are based, as first-line treatment, on the administration of the vascular endothelial growth factor (VEGF) neutralizing antibody termed Bevacizumab. Despite proven benefits, the expected results were not obtained for the majority of patients. The possibility that an intricate interplay between angiogenesis and immune-checkpoints might exist lead us to evaluate tumor angiogenesis, by means of VEGF expression together with the immune checkpoint HLA-G/ILT4. METHODS: Tumor specimens were obtained from patients from two separate cohorts: One from "Evita Pueblo" Hospital from Berazategui, (Buenos Aires, Argentina) and the second includes patients surgically operated at the Urology Department of Saint-Louis Hospital (Paris, France) with a confirmed ccRCC diagnosis. Immunohistochemistry was performed with specific antibodies directed against HLA-G, VEGF-A, VEGF-C, D240, CD34, ILT4 and Ca-IX. In addition, gene expression levels were measured in a cell line derived from a ccRCC patient by semi-quantitative RT-PCR. RESULTS: Our results show that the highly vascularized tumors of ccRCC patients express high levels of VEGF and the immune-checkpoint HLA-G. In addition, ILT4, one of the HLA-G receptors, was detected on macrophages surrounding tumor cells, suggesting the generation of an immune-tolerant microenvironment that might favor tumorigenesis. Notably, RT-qPCR analysis provided the first evidence on the transcriptional relationship between HLA-G/ILT4 and the VEGF family. Namely, in the presence of HLA-G or ILT4, the levels of VEGF-A are diminished whereas those of VEGF-C are increased. CONCLUSIONS: In an effort to find new therapeutic molecules and fight against metastasis dissemination associated with the poor survival rates of ccRCC patients, these findings provide the rationale for co-targeting angiogenesis and the immune checkpoint HLA-G.
Subject(s)
Carcinoma, Renal Cell/genetics , HLA-G Antigens/metabolism , Kidney Neoplasms/genetics , Membrane Glycoproteins/metabolism , Neovascularization, Pathologic/genetics , Receptors, Immunologic/metabolism , Vascular Endothelial Growth Factor A/genetics , Adult , Aged , Angiogenesis Inhibitors/pharmacology , Angiogenesis Inhibitors/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/pharmacology , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Renal Cell/immunology , Carcinoma, Renal Cell/mortality , Carcinoma, Renal Cell/therapy , Cell Line, Tumor , Female , Gene Expression Regulation, Neoplastic/drug effects , Gene Expression Regulation, Neoplastic/immunology , Humans , Immune Checkpoint Inhibitors/pharmacology , Immune Checkpoint Inhibitors/therapeutic use , Kidney/blood supply , Kidney/pathology , Kidney/surgery , Kidney Neoplasms/immunology , Kidney Neoplasms/mortality , Kidney Neoplasms/therapy , Male , Membrane Glycoproteins/antagonists & inhibitors , Middle Aged , Neovascularization, Pathologic/drug therapy , Neovascularization, Pathologic/pathology , Nephrectomy , Receptors, Immunologic/antagonists & inhibitors , Retrospective Studies , Survival Rate , Vascular Endothelial Growth Factor A/antagonists & inhibitorsABSTRACT
OBJECTIVES: To assess initial and long-term outcome of children with persistent/chronic idiopathic thrombocytopenic purpura (ITP) treated with 4 infusions of rituximab and three 4-day cycles of dexamethasone (4R+3Dex) including cohorts with most benefit and/or treatment associated toxicity. STUDY DESIGN: All pediatric patients with ITP at Weill-Cornell who received 4R+3Dex were included in this retrospective study. Duration was median time from first rituximab infusion to treatment failure. Patient cohort included 33 children ages 1-18 years with persistent/chronic ITP; 19 were female, 10 of whom were adolescents. Every patient had failed more than 1 and usually several ITP treatments. RESULTS: Children were treated with rituximab, 375 mg/m2 weekly for 4 weeks and three 4-day courses of dexamethasone 28 mg/m2 (40 mg max). Average age of nonresponders was 7.75 years, and initial responders averaged 12.7 years (P = .0073); 30% maintained continuing response at 60 months or last check-up. Eight of the 10 patients who underwent remission were female with ITP <24 months prior to initiating 4R+3Dex. All responding male patients except 2 relapsed. CONCLUSIONS: Durable unmaintained ITP remission after 4R+3Dex was seen almost exclusively in female adolescents with <24 months duration of ITP. This provides a new therapeutic paradigm for a subpopulation with hard-to-treat chronic ITP. The pathophysiology of ITP underlying this distinction requires further elucidation.
Subject(s)
Anti-Inflammatory Agents/administration & dosage , Dexamethasone/administration & dosage , Immunologic Factors/administration & dosage , Purpura, Thrombocytopenic, Idiopathic/drug therapy , Rituximab/administration & dosage , Adolescent , Anti-Inflammatory Agents/therapeutic use , Child , Child, Preschool , Chronic Disease , Dexamethasone/therapeutic use , Drug Administration Schedule , Drug Therapy, Combination , Female , Follow-Up Studies , Humans , Immunologic Factors/therapeutic use , Infant , Infusions, Intravenous , Male , Retrospective Studies , Rituximab/therapeutic use , Treatment OutcomeABSTRACT
We performed a retrospective genome-wide association study in HIV-infected individuals who were treated with dendritic cell-based immunotherapy in clinical trials performed by two research groups (Spain and Brazil). We aimed to identify host genetic variants influencing treatment response. The Illumina Human Core Exome 12 v 1.0 Bead Chip with over 250,000 markers was used to analyze genetic factors affecting treatment response. Additionally, we performed a meta-analysis of the results obtained from Spanish and Brazilian patients. We identified a genetic variation (rs7935564 G allele) in TRIM22 gene, which encodes TRIM22 protein acting like a HIV restriction factor, as being associated with good response to dendritic cell-based immunotherapy. We then verified the impact of TRIM22 rs7935564 SNP in susceptibility to HIV infection and disease progression by assessing the influence of biogeographic ancestry in the distribution of allelic and genotype frequencies in three populations from Italy, Brazil and Zambia. TRIM22 rs7935564 genotyping indicated association of G rs7935564 allele with long-term non-progression of HIV disease in Italian patients, thus corroborating our hypothesis that it is involved as a restriction factor in dendritic cell-based immunotherapy response. TRIM22 rs7935564 polymorphism was associated with good response to dendritic cell-based immunotherapy. We hypothesize that in selecting patients for treatment, there is a possible bias related to the natural presence of restriction factors that are genetically determined and could influence final outcome of therapy.
Subject(s)
Dendritic Cells/immunology , HIV Infections/therapy , HIV-1/immunology , Immunotherapy/methods , Minor Histocompatibility Antigens/genetics , Repressor Proteins/genetics , Tripartite Motif Proteins/genetics , Adult , Brazil , Child , Dendritic Cells/transplantation , Female , Gene Frequency , Genetic Predisposition to Disease , Genome-Wide Association Study , Genotype , HIV Infections/immunology , Humans , Italy , Male , Polymorphism, Single Nucleotide , Retrospective Studies , Spain , Treatment OutcomeABSTRACT
Abstract The epithelial ovarian cancer (EOC) has been underdiagnosed because it does not have a specific clinical presentation, and the signs and symptoms are similar to the irritable bowel syndrome and pelvic inflammatory disease. EOC is less common than breast and cervical cancer, but it is more lethal. On the whole, EOC has an early dissemination to peritoneal cavity, which delays a timely diagnosis and increases the rate of advanced diagnosed disease. The diagnosis usually surprises the women and the primary care physician. Therefore, it is necessary to count on prevention and early diagnosis programs. EOC has 80% response to surgical treatment, but nearly 70% of the patients may relapse in five years. The objectives of this document are presenting a summary of the EOC epidemiology and comment about advancements in prevention, diagnosis, and treatment of this cancer. That will raise awareness about the importance of this disease.
Resumen El cáncer ovárico epitelial (COE) ha sido subdiagnosticado debido a que no tiene presentación clínica específica y a que los signos y síntomas son similares al síndrome de colon irritable y a la enfermedad inflamatoria pélvica. Es menos común que el cáncer de mama o el cervicouterino, pero es más letal. En general, tiene diseminación temprana a cavidad peritoneal, lo cual retrasa un pronóstico oportuno e incrementa la tasa de diagnóstico de enfermedad avanzada. Usualmente, el diagnóstico sorprende a la mujer y al médico de primer contacto. Entonces, es necesario contar con programas de prevención y diagnóstico temprano. El COE tiene 80% de respuesta quirúrgica, pero cerca de 70% de las pacientes puede recaer en cinco años. Los objetivos de este documento son presentar un resumen de la epidemiología del COE y comentar los avances en prevención, diagnóstico y tratamiento de este cáncer. Esto despertará la conciencia acerca de la importancia de esta enfermedad.
Subject(s)
Humans , Female , Adult , Middle Aged , Aged , Aged, 80 and over , Young Adult , Ovarian Neoplasms/epidemiology , Carcinoma/epidemiology , Ovarian Neoplasms/therapy , Peritoneal Neoplasms/secondary , Carcinoma/diagnosis , Carcinoma/therapy , Ovariectomy , Combined Modality Therapy , Early Detection of Cancer , Immunotherapy , Mexico/epidemiology , Neoplasm StagingABSTRACT
Despite the existence of effective prophylactic vaccines, hepatitis B virus (HBV) infections remain a major public health problem. It has been estimated that about 370 million people are chronically infected with this virus worldwide. These individuals act as a reservoir for viral spread and chronic infection also increases the risk of liver diseases, such as cirrhosis and hepatocellular carcinoma. Current antiviral therapies fail to control viral replication in the long term in most patients. Viral persistence has been associated with a defect in the development of HBV-specific cellular immunity. The limitations of the current available therapies underline the need for alternative therapies. Specific immunotherapeutic strategies target not only the induction or stimulation of CD4(+) and CD8(+) T-cell responses but also the induction of proinflammatory cytokines capable of controlling viral replication. Therapeutic vaccination has been extensively studied in chronic hepatitis B (CHB) based in the properties of hepatitis B surface antigen (HBsAg) and taking advantage of its previous use in preventive vaccination. In this sense, pioneer studies were carried out employing HBsAg-based vaccines, including prophylactic commercial vaccines and HBsAg-based formulations with novel adjuvants. The results and general knowledge coming from these studies are discussed in the present review. The decision on developing new generations of vaccines including new antigens or formulations should take into account the experience with HBsAg-based vaccine formulations in order to decide about changing the vaccine antigen or adding new antigens to improve the composition. How to cite this article: Aguilar JC, Lobaina Y. Immunotherapy for Chronic Hepatitis B using HBsAg-based Vaccine Formulations: From Preventive Commercial Vaccines to Therapeutic Approach. Euroasian J Hepato-Gastroenterol 2014;4(2):92-97.